Persistant neurogenesis in the adult brain is an exciting phenomena because of the promise it holds for developing therapeutics to treat diseased and injured central nervous systems (CNS). Unfortunately, how neural stem cells are stimulated to proliferate and differentiate into a various cell types and how their progeny can be induced to survive in the adult brain are not understood. Moreover, rapid means for testing candidate genes in these processes in the intact mammalian CNS are lacking. For the proposed project, genes whose knock down revealed cell loss phenotypes in a recent genome-wide RNA interference (RNAi) screen accomplished in the Perrimon lab will be examined for roles in neural cell survival, cell number, and differentiation. The screen was performed using Drosophila primary cultures of neurons, glia, and muscle cells.(K. Sepp and N. Perrimon, in preparation). Genes in this unique data set are candidates for neural-cell specific proliferation, fate determination, or viability because they were not uncovered in more general screens for cell loss in non-neural cell lines performed in the Perrimon laboratory. Secondary assays and genetic approaches in vivo will be used to identify how knockdown of these genes brings about neural-specific cell loss. Findings will be immediately applied to studies of vertebrate neurogenesis by taking advantage of a rapid in vivo RNAi assay to test the genes for roles in progenitor cell proliferation or survival in the mouse retina. This study is expected to lead to the discovery of novel therapeutic targets for intervention in cases of retinal degeneration and may have more widespread implications brain injury and disease. [unreadable] [unreadable]